ArticleCPT: pharmacometrics & systems pharmacology2013
Systems pharmacology models can be used to understand complex pharmacokinetic-pharmacodynamic behavior: an example using 5-lipoxygenase inhibitors.
Article in CPT: pharmacometrics & systems pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- AI-based identification of therapeutic agents targeting GPCRs: introducing ligand type classifiers and systems biology.Chemical science · 2023Article
- A QSP model of prostate cancer immunotherapy to identify effective combination therapies.Scientific reports · 2020Article
- gQSPSim: A SimBiology-Based GUI for Standardized QSP Model Development and Application.CPT: pharmacometrics & systems pharmacology · 2020Article
- Quantitative Systems Pharmacology: An Exemplar Model-Building Workflow With Applications in Cardiovascular, Metabolic, and Oncology Drug Development.CPT: pharmacometrics & systems pharmacology · 2019Review
- Automated Scale Reduction of Nonlinear QSP Models With an Illustrative Application to a Bone Biology System.CPT: pharmacometrics & systems pharmacology · 2018Article
- Quantitative Systems Pharmacology Modeling of Acid Sphingomyelinase Deficiency and the Enzyme Replacement Therapy Olipudase Alfa Is an Innovative Tool for Linking Pathophysiology and Pharmacology.CPT: pharmacometrics & systems pharmacology · 2018Article
- Preclinical QSP Modeling in the Pharmaceutical Industry: An IQ Consortium Survey Examining the Current Landscape.CPT: pharmacometrics & systems pharmacology · 2018Review
- Using quantitative systems pharmacology to evaluate the drug efficacy of COX-2 and 5-LOX inhibitors in therapeutic situations.NPJ systems biology and applications · 2018Article
- Selection and Qualification of Simplified QSP Models When Using Model Order Reduction Techniques.The AAPS journal · 2017Article
- A Mathematical Modeling Approach to Understanding the Effect of Anti-Interleukin Therapy on Eosinophils.CPT: pharmacometrics & systems pharmacology · 2016Article
- A model qualification method for mechanistic physiological QSP models to support model-informed drug development.CPT: pharmacometrics & systems pharmacology · 2016Article
- The promises of quantitative systems pharmacology modelling for drug development.Computational and structural biotechnology journal · 2016Review
- Dynamic model of eicosanoid production with special reference to non-steroidal anti-inflammatory drug-triggered hypersensitivity.IET systems biology · 2015Article
- BioModels: Content, Features, Functionality, and Use.CPT: pharmacometrics & systems pharmacology · 2015Article
- Systems pharmacology approaches for optimization of antiangiogenic therapies: challenges and opportunities.Frontiers in pharmacology · 2015Article
- Implementation of quantitative and systems pharmacology in large pharma.CPT: pharmacometrics & systems pharmacology · 2014Review
- Evaluating systems pharmacology models is different from evaluating standard pharmacokinetic-pharmacodynamic models.CPT: pharmacometrics & systems pharmacology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zileuton, a 5-lipoxygenase (5LO) inhibitor, displays complex pharmaokinetic (PK)-pharmacodynamic (PD) behavior. Available clinical data indicate a lack of dose-bronchodilatory response during initial treatment, with a dose response developing after ~1-2 weeks. We developed a quantitative systems pharmacology (QSP) model to understand the mechanism behind this phenomenon. The model described the release, maturation, and trafficking of eosinophils into the airways, leukotriene synthesis by the 5LO enzyme, leukotriene signaling and bronchodilation, and the PK of zileuton. The model provided a plausible explanation for the two-phase bronchodilatory effect of zileuton-the short-term bronchodilation was due to leukotriene inhibition and the long-term bronchodilation was due to inflammatory cell infiltration blockade. The model also indicated that the theoretical maximum bronchodilation of both 5LO inhibition and leukotriene receptor blockade is likely similar. QSP modeling provided interesting insights into the effects of leukotriene modulation.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e74; doi:10.1038/psp.2013.49; advance online publication 11 September 2013.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.